Fatty Acid Metabolism

Question 1

Lipoprotein Lipase

Answer 1

takes FFA from chylomicrons (hydrolyzes triglycerides–> FFA + monoacylglycerol) in vessel wall and imports them into adipose or muscle tissue

In fed state – increased LPL in adipose tissue
in fasted/exercise state– increased LPL in

lactating– increased LPL in mammary gland

Question 2

Carnitine shuttle

Answer 2

FFA access into mitochodnrial atrix to undergo b-ox since mitochondrial membranes are impermeable to FFAs.

Fatty Acyl CoA synthetase– converts FFA + CoA into FA-CoA across outer membrane

CPT I/II- carnitine palm. transferase

translocase

Question 3

B-oxidation per cycle

Answer 3

NADH x1
FADH x1
Acetyl-CoA (2 C’s)

ex: 16 C FA –> 8 acetyl CoA + 7 FADH2’s

Question 4

Oxidation of very long chain FA

Answer 4

converted to octanoyl-CoA (8 C FA) in peroxysomes

Question 5

Final product B-oxidation

Answer 5

FA-CoA + acetyl-CoA

Question 6

Zellweger Syndrome

Answer 6

defect in peroxisome biogenesis that affects all tissues

Question 7

X-linked adrenoleukodystrophy

Answer 7

ability of VLCFA to cross peroxisome membrane –> accumulatio of VLCFAs in blood and tissues –> results in:

1. decrease in plamalogens
2. adrenocortical insufficiency
3. abnormalities in white matter of cerebrum

Question 8

Medium chain acyl-CoA DH deficiency

Answer 8

Causes: Akee fruit (jamaca), 2 copies mutant MCAD allele

consequences: decreased ability of FA to serve as fuel, gluconeogenesis shut down because pyruvate carboxylase depends on acetyl CoA

HIGH LEVELS C6-C10 dicarboxylic acids in urine, increased acyl carnitine levels

increased FA in plasma, fat in liver

TREATMENT: IF genetic defect detected after birth

Question 9

Carnitine Deficiency (Carnitine acyl transferase deficiency)

Answer 9

inability to transport LCFA –> mitochondria

consequences– increased FA in blood
hypoglycemia
low levels ketones
impaired gluconeogenesis

treatment- high doses carnitine

Question 10

oxidation of odd chain FA

Answer 10

propionyl-CoA –>
[PROPIONYL-COA CARBOXYLASE//BIOTIN] –> Mehylmalonyl-CoA –>
[METHYLMALONYL-COA MUTASE//B12] –> succinyl CoA

Question 11

Methylmalonic acidemia

Answer 11

defective methylmalonyl CoA mutase (converts methylmalonyl CoA –> succinyl CoA) in oxidation of odd chain FA

deficiency of B12

treatment = adenosyl cobalamine

Question 12

Refsum’s

Answer 12

accumulationof phytanic acid.

dietary restriciton of green veggies and milk and meet

peroxisomal disorder caused by impaired alpha-oxidation of branched fatty acids which leads to an increase in phytanic acid

Question 13

b-hydroxybutyrate

Answer 13

major plasma ketone body

ketone bodies are a source of fuel in starvation state.

ketone bodies formed in liver

can be synthesized in mitochondria– same beginning steps as cholesterol –> forms HMG-CoA –> –> b-hydroxybutyrate

Question 14

Rate limiting step for fatty acid synthesis

Answer 14

acetyl coa + bicarb –> acetyl coa carboxylase//biotin//CITRATE –> malonyl CoA

inactivated by palmitoyl coA